Low Estradiol Level and Endometrial Thickness on the Day of Endometrial Transformation Influence Clinical Pregnancy After Intrauterine Insemination.

Background: The causes of pregnancy failure after intrauterine insemination (IUI) are controversial. The purpose of this study was to investigate the influencing factors on clinical pregnancy after IUI. Methods: This study retrospectively analyzed 1464 cycles of IUI performed at the Meizhou People's Hospital between March 2014 and June 2023. The χ2 test and logistic regression analysis was applied to assess the associations between the some factors (maternal age, paternal age, cycle type (natural cycle or ovulation induction cycle), hormone level on the day of endometrial transformation (estradiol (E2), luteinizing hormone (LH), and progesterone (P)), endometrial thickness on the day of endometrial transformation, and forward motile sperm concentration after treatment) and pregnancy failure. Results: Among the 1464 IUI cycles in this study, 268 cycles of assisted reproduction resulted in clinical pregnancy, with a clinical pregnancy rate of 18.3%. During the cycles with clinical pregnancy, there were 25 (12.9%) preterm births and 169 (87.1%) full-term births. The E2 level on the day of endometrial transformation in clinical pregnancy group was higher than that in the pregnancy failure group (658.79±656.02 vs 561.21±558.83 pg/mL)(P=0.025). The clinical pregnancy group had a higher percentage of endometrial thickness between 8 and 13mm on the day of endometrial transformation than the pregnancy failure group (83.2% vs 75.0%)(P=0.002). The results of regressions analysis showed that low E2 level on the day of endometrial transformation (<238.3 pg/mL vs ≥238.3 pg/mL: OR 1.493, 95% CI: 1.086-2.052, P=0.014), and endometrial thickness <8mm on the day of endometrial transformation (<8mm vs 8-13mm: OR 1.886, 95% CI: 1.284-2.771, P=0.001) may increase risk of pregnancy failure performed IUI. Conclusion: Low estradiol level, and endometrial thickness on the day of endometrial transformation may increase risk of pregnancy failure performed intrauterine insemination.

Tspan5 promotes the EMT process to regulate the syncytialization of trophoblast cells by activating Notch signalling.

Placental trophoblastic cells play important roles in placental development and fetal health. However, the mechanism of trophoblastic cell fusion is still not entirely clear. The level of Tspan5 in the embryo culture medium was detected using enzyme-linked immunosorbent assay (ELISA). Fusion of BeWo cells was observed by immunofluorescence. Cell fusion-related factors and EMT-related factors were identified by qRT-PCR and western blotting. Notch protein repressor DAPT was used to verify the role of Tspan5 in BeWo cells. The expression of Tspan5 was significantly increased in embryo culture medium. The fusion of BeWo cells was observed after treatment with forskolin (FSK). Cell fusion-related factors (i.e. ß-hCG and syncytin 1/2) and Tspan5 were significantly increased after FSK treatment. In addition, FSK treatment promoted EMT-related protein expression in BeWo cells. Knockdown of Tspan5 inhibited cell fusion and EMT-related protein levels. Notch-1 and Jagged-1 protein levels were significantly upregulated, and the EMT process was activated by overexpression of Tspan5 in FSK-treated BeWo cells. Interestingly, blocking the Notch pathway by the repressor DAPT had the opposite results. These results indicated that Tspan5 could promote the EMT process by activating the Notch pathway, thereby causing cell fusion. These findings contribute to a better understanding of trophoblast cell syncytialization and embryonic development. Tspan5 may be used as a therapeutic target for normal placental development.

Risk Factors of Preterm Birth and Low Birth Weight in Singletons Conceived Through Frozen Embryo Transfer: A Retrospective Study.

Background: The risks of adverse perinatal outcomes in offspring conceived following frozen-thawed embryo transfer (FET) assisted reproductive technology (ART) are inconsistent. The aim of this study was to analyze the risk factors for preterm birth and low birth weight in singletons after FET. Methods: 386 FET cycles was conducted at the Reproductive Medicine Center of Meizhou People's Hospital. The relationship between clinical characteristics and outcomes (term birth and preterm birth, normal birth weight and low birth weight) was analyzed. Results: The rate of primary infertility, basal FSH and T levels, gestational age, birth weight, and proportion of male fetuses were significantly different in the preterm and full-term groups. Logistic regression analysis showed that high maternal age (≥35 years) (OR 3.652, 95% CI: 1.683-7.925, P=0.001), primary infertility (OR 2.869, 95% CI: 1.461-5.632, P=0.002), low FSH level (<6.215 mIU/mL) (OR 3.272, 95% CI: 1.743-6.144, P<0.001), and hormone replacement therapy (HRT) method (OR 2.780, 95% CI: 1.088-7.100, P=0.033) may increase risk of preterm birth after FET. Gestational age and birth weight were significantly different in fetuses with low birth weight (<2500g, n=38) and normal birth weight (≥2500g and <4000g, n=333). Logistic regression analysis showed that low basal FSH level (<6.215 mIU/mL) (OR 0.425, 95% CI: 0.209-0.865, P=0.018), and HRT method of endometrial preparation for FET (OR 0.272, 95% CI: 0.079-0.934, P=0.039) may reduce the risk of low birth weight after FET. Conclusion: High maternal age, primary infertility, low FSH level, HRT method of endometrial preparation for FET, and male fetus may increase risk of preterm birth after FET. In addition, primary infertility, low basal FSH level, and HRT method of endometrial preparation may reduce the risk of low birth weight after FET.

Risk Factors of Pregnancy Failure in Infertile Patients Undergoing Assisted Reproductive Technology.

Background: Infertile couples need to use assisted reproductive technology (ART) to give birth. However, pregnancy failure after ART is not uncommon. At present, the results of studies on the causes of pregnancy failure after ART are inconsistent. Methods: A retrospective cohort study involving 715 embryo transfer cycles was conducted at the Reproductive Medicine Center of Meizhou People's Hospital, from December 2015 to June 2022. According to the pregnancy, they were divided into clinical pregnancy group and pregnancy failure group. The relationship between demographic characteristics and pregnancy status between the two groups was analyzed. Results: The pregnancy failure rate after ART was 49.7% (355/715). There were statistically significant distribution differences of maternal age, paternal age, COH protocols, and number of embryos transferred between clinical pregnancy and pregnancy failure groups (all P<0.01). Multiple logistic regression analysis shows that high maternal age (>35 years old vs ≤35 years old: OR 2.173, 95% CI: 1.386-3.407, P=0.001), and GnRH-a short protocol (GnRH-a short protocol vs GnRH-a long protocol: OR 2.139, 95% CI: 1.127-4.058, P=0.020) may increase risk of pregnancy failure in ART pregnancies, while two embryos transferred (two embryos transferred vs one embryo transferred: OR 0.563, 95% CI: 0.377-0.839, P=0.005) may reduce risk of pregnancy failure. In addition, high maternal age, GnRH antagonist protocol, and GnRH-a short protocol may increase risk of implantation failure, while two embryos transferred may reduce risk of implantation failure. And high maternal age may increase risk of biochemical pregnancy. Conclusion: The risk of pregnancy failure increased in ART cycles with maternal age >35 years old and GnRH-a short protocol, while reduced with two embryos transferred.

Vam3, a Compound Derived from Vitis amurensis Rupr., Attenuated Colitis-Related Tumorigenesis by Inhibiting NF-κB Signaling Pathway.

BACKGROUND: Chronic inflammation is one of the important mediators of colitis-related colon cancer (CRC). Abundant mast cells (MCs) were observed in the tumor microenvironment and mediators released upon MC activation play an important role in the process of chronic inflammation. Previously, we found that activation of intestine mucosal MCs recruited and modulated the inflammatory CD11b(+)Gr1(+) cells to promote the CRC development. In the current study we investigated the effects of Vam3, a resveratrol dimer with potent anti-inflammatory effects, on CRC development. METHODS: RBL-2H3 cells, a basophilic leukemia cell line, were pretreated with 2.5 or 5 µM Vam3 and then stimulated with dinitrophenol-conjugated bovine serum albumin (DNP-BSA) plus lipopolysaccharide (LPS). The MC degranulation was determined by measuring ß-hexosaminidase release. Generation of TNF-α and IL-6 in RBL-2H3 cells or in peritoneal macrophages was determined by ELISA and real-time qPCR. NF-κB p65 and phospho-NF-κB p65 expression was determined by Western blotting. NF-κB activity in RAW264.7 cells was determined by luciferase reporter assay. CRC was induced in C57BL/6 mice by intraperitoneal injection of azoxymethane (AOM), followed by oral exposure to dextran sodium sulfate (DSS). Vam3 at 50 mg/kg, or disodium cromoglycate (DSCG, MC stabilizer) at 100 mg/kg, or vehicle were administrated to the mice 4 weeks after DSS withdrawal. Levels of TNF-α, IL-6, and mouse MC protease-1 were determined by ELISA. Infiltration of CD11b(+)Gr1(+) cells was determined by flow cytometry analysis. One-way ANOVA was used to compare difference between groups. RESULTS: Pretreatment with Vam3 significantly inhibited RBL-2H3 cell degranulation and inflammatory cytokine production from RBL-2H3 cells and from peritoneal macrophages. After Vam3 treatment, NF-κB activity in RAW264.7 cells, and expressions of phospho-NF-κB p65 in RBL-2H3 cells and in peritoneal macrophages were significantly down-regulated. In the AOM plus DSS-induced CRC murine model, the Vam3 and DSCG-treated mice had less tumor numbers than those treated with vehicle. Expression of phospho-NF-κB p65, production of inflammatory cytokines, and infiltration of MCs and CD11b(+)Gr1(+) cells were attenuated in the Vam3-treated mice. CONCLUSION: Vam3 treatment could attenuate the CRC development. This effect may be due to its inhibition on NF-κB signaling pathway in MCs and macrophages of the inflamed intestines.

Activation of mucosal mast cells promotes inflammation-related colon cancer development through recruiting and modulating inflammatory CD11b(+)Gr1(+) cells.

Mast cells (MCs) have been reported to be one of the important immunoregulatory cells in promoting the development of colitis-related colon cancer (CRC). It is not clear which MC subtypes play critical roles in CRC progression from colitis to cancer because mucosal mast cells (MMCs) are distinct from connective tissue mast cells (CTMCs) in maintaining intestinal barrier function under homeostatic and inflammatory conditions. In the current study, we found that MMC numbers and the gene expressions of MMC-specific proteases increased significantly in an induced CRC murine model. The production of mast cell protease-1 (mMCP-1) after MMC activation not only resulted in the accumulation of CD11b(+)Gr1(+) inflammatory cells in the colon tissues but also modulated the activities of CD11b(+)Gr1(+) cells to support tumor cell growth and to inhibit T cell activation. Blocking the MMC activity in mice that had developed colitis-related epithelium dysplasia, CD11b(+)Gr1(+) infiltration was reduced and CRC development was inhibited. Our results suggest that MMC activation recruited and modulated the CD11b(+)Gr1(+) cells to promote CRC and that MMCs can be potential therapeutic targets for the prevention of CRC development.

Maternal transmission risk and antibody levels against hepatitis B virus e antigen in pregnant women.

BACKGROUND: The generation of antibodies (anti-HBe) against hepatitis B virus (HBV) e antigen (HBeAg) often coincides with clinical remission in chronic HBV patients. We aimed to examine the effect of maternal anti-HBe in protection against HBV mother-to-child transmission (MTCT). METHODS: A total of 140 chronic HBV-infected pregnant women participated in this study. Before delivery, maternal HBV serological markers and HBV viral load were determined and anti-HBe titers were semi-quantified. Neonatal hepatitis B surface antigen (HBsAg) and HBV-DNA status were determined from cord blood. The children were followed to age 1-3 years. RESULTS: The HBV-DNA positive rate in cord blood was 75.61% (31/41) in those who were born to mothers with serum HBV-DNA >10(6) IU/ml, which was significantly higher than in those who were born to mothers with HBV-DNA <10(6) IU/ml (3/99, 3.03%; p<0.0001). However, 10 newborns from mothers with serum HBV-DNA >10(6) IU/ml had no detectable HBV-DNA in cord blood; anti-HBe was positive with a median titer of 10 (interquartile range 10-55). A total of 84 children who received hepatitis B immune globulin (HBIG) within 12h after birth and who completed three doses of recombinant HBV vaccination were followed to age 1-3 years (up to May 2014). All 56 children who were born to mothers with serum HBV-DNA levels <10(6) IU/ml were HBsAg-negative. Five of the 22 children born to anti-HBe-negative mothers with serum HBV-DNA >10(6) IU/ml acquired an HBsAg-positive status. However, none of the six children who were born to anti-HBe-positive/weak-positive mothers with serum HBV-DNA >10(6) IU/ml acquired an HBsAg-positive status. CONCLUSIONS: The presence of maternal anti-HBe is protective against HBV MTCT, independent of the maternal serum HBV viral load.